Zwitterion-Modified MXene Quantum Dot as a Nanocarrier for Traditional Chinese Medicine Sanguinarine Delivery and Its Application for Photothermal-Chemotherapy Synergistic Antibacterial and Wound Healing.

The nanomaterialization of traditional Chinese medicine (TCM) has aroused widespread interest among researchers. Sanguinarine (SAN) is a kind of TCM with good antibacterial properties, which has important applications in anti-infection of wounds. Additionally, the combination of photothermal therapy and chemotherapy can overcome bacterial resistance, further improving bactericidal and wound healing efficiency. In this paper, we prepared an antibacterial agent by loading SAN on the zwitterion-modified MXene quantum dot nanocarrier (SAN@AHEP@Ta4C3), realizing pH/NIR controlled drug release and photothermal/chemotherapy synergistic antibacterial and wound healing. The particle size of SAN@AHEP@Ta4C3 is about 120 nm, and it has a good water solubility and stability. In addition, it also has excellent photothermal conversion performance (η = 39.2%), which can effectively convert light energy into heat energy under near-infrared (NIR) laser irradiation, further promoting drug release and achieving bactericidal effects by synergistic chemotherapy and photothermal therapy. The in vitro and in vivo experiments show that SAN@AHEP@Ta4C3 exhibits an excellent antibacterial effect against Staphylococcus aureus and Escherichia coli, and it can effectively promote the wound healing of mice. Moreover, the SAN@AHEP@Ta4C3 also has good biocompatibility and has no side effects on normal tissue and organs. This work introduces a multifunctional antibacterial agent based on TCM and hot-spot material MXene, which will have considerable application prospects in biomedical fields.

Biomedical Application of Decellularized Scaffolds.

Tissue loss and end-stage organ failure are serious health problems across the world. Natural and synthetic polymer scaffold material based artificial organs play an important role in the field of tissue engineering and organ regeneration, but they are not from the body and may cause side effects such as rejection. In recent years, the biomimetic decellularized scaffold based materials have drawn great attention in the tissue engineering field for their good biocompatibility, easy modification, and excellent organism adaptability. Therefore, in this review, we comprehensively summarize the application of decellularized scaffolds in tissue engineering and biomedicine in recent years. The preparation methods, modification strategies, construction of artificial tissues, and application in biomedical applications are discussed. We hope that this review will provide a useful reference for research on decellularized scaffolds and promote their application tissue engineering.

An iron(III) complex-based supramolecular organic framework (SOF) as a theranostic platform via magnetic resonance imaging-guided chemotherapy.

It is crucially important to explore the additional metal-endowed functions of supramolecular organic frameworks (SOFs) for expanding their applications. In this work we have reported the performance of a SOF (designated as Fe(III)-SOF) as a theranostic platform via magnetic resonance imaging (MRI)-guided chemotherapy. The Fe(III)-SOF may be used as an MRI contrast agent for cancer diagnosis because the building unit (iron complex) contains high spin iron(III) ions. Additionally, the Fe(III)-SOF may also be used as a drug carrier because it possesses stable internal voids. We loaded doxorubicin (DOX) into the Fe(III)-SOF to obtain a DOX@Fe(III)-SOF. The Fe(III)-SOF showed good loading content (16.3%) and high loading efficiency (65.2%) for DOX. Additionally, the DOX@Fe(III)-SOF had a relatively modest relaxivity value (r2 = 19.745 mM-1 s-1) and exhibited the strongest negative contrast (darkest) at 12 h of post-injection. Furthermore, the DOX@Fe(III)-SOF effectively inhibited tumor growth and showed high anticancer efficiency. In addition, the Fe(III)-SOF was biocompatible and biosafe. Therefore, the Fe(III)-SOF was an excellent theranostic platform and may have potential applications in tumor diagnosis and treatment in the future. We believe that this work will initiate extensive research endeavors not only on the development of SOFs, but also on the construction of theranostic platforms based on SOFs.

Decellularized Scaffold-Based Artificial Vascular Patch for Porcine Vascular Repair.

Vascular transplantation is an effective strategy against cardiovascular diseases (CVD), and artificial vascular patches are of urgent need across the world. In this work, we designed a multifunctional decellularized scaffolds (DCS)-based vascular patch for porcine vascular repair. Ammonium phosphate zwitter-ion (APZI) and poly(vinyl alcohol) (PVA) hydrogel were coated on the surface of DCS to improve the mechanical properties and biocompatibility of an artificial vascular patch. Then a heparin (Hep)-loaded metal-organic framework (MOF) further decorated the artificial vascular patches to inhibit blood coagulation and promote vascular endothelialization. The obtained artificial vascular patch showed suitable mechanical properties, good biocompatibility, and blood compatibility. In addition, the proliferation and adhesion of endothelial progenitor cells (EPCs) on the surface of artificial vascular patch improved a lot when compared with unmodified PVA/DCS. According to the results of B-ultrasound and CT images, the artificial vascular patch could maintain the patency of the implant site after implanting into the pig carotid artery. The current results solidly support that a MOF-Hep/APZI-PVA/DCS vascular patch would be an excellent vascular replacement material.

Enhanced and sustained pesticidal activity of a graphene-based pesticide delivery system against the diamondback moth Plutella xylostella.

BACKGROUND: Traditional abamectin (Abm) formulations have several shortcomings, such as low water solubility, burst release behavior, poor photostability, and short persistence periods, which decrease their pesticidal activity and the risks they pose to the environment. Nanomaterial-based pesticide delivery systems (PDSs) provide new strategies for the efficient and safe application of pesticides. Here, we developed Abm-loaded graphene oxide (Abm/GO) as a PDS for the sustained release of Abm, which shows enhanced control efficacy against Plutella xylostella. RESULTS: The hydrophobic Abm molecule was effectively loaded on GO nanocarrier by a physisorption method, which formed a uniform and stable Abm/GO nanoformulation. GO possesses high adsorption capacity and can effectively load Abm. The Abm/GO nanoformulation shows enhanced water dispersion stability and can remain stable during a 2-year storage period in contrast to the water-insoluble Abm. In addition, the Abm/GO nanoformulation exhibits sustained pesticide release behavior and possesses significantly improved anti-ultraviolet properties. Thus, the Abm/GO nanoformulation shows superior pesticidal activity compared with Abm. Abm/GO showed negligible toxicity to maize seedlings, and its GO nanocarrier can reduce the cytotoxicity of Abm to A549 cells. CONCLUSION: GO-based PDSs can effectively overcome the disadvantages of traditional pesticides, such as their insolubility, burst release behavior, instability, and short persistence period. GO shows much future promise in agriculture in light of its industrialization potential. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Carboxymethyl Chitosan-Modified Graphene Oxide as a Multifunctional Vector for Deltamethrin Delivery and pH-Responsive Controlled Release, Enhanced Leaf Affinity, and Improved Mosquito-Killing Activity.

Traditional deltamethrin (DM) formulations (e.g., emulsifiable concentrates, wettable powders, etc.) have significant disadvantages of poor water dispersion stability, burst release, weak leaf affinity, short duration, poor efficacy, and high environmental toxicity. A nanomaterial-based pesticide delivery system (PDS) has provided effective strategies for green preparation and synergism of pesticide formulations. In this article, we developed carboxymethyl chitosan (CMCS)-modified graphene oxide (GO) as a vector for DM and constructed a pH-responsive PDS for Culex pipiens pallens control. GO-CMCS possesses excellent pesticide loading performance for DM (loading rate 87.76%). After being loading on GO-CMCS, the GO-CMCS-DM has a significantly improved dispersion stability in water. The GO-CMCS-DM exhibits pH-responsive controlled release performance, which can sustain the release of DM into the medium, maintaining an effective long-term concentration. Additionally, the leaf adhesion of GO-CMCS-DM is better than that for free DM, which can improve the pesticide utilization. Therefore, GO-CMCS-DM has a prolonged persistent period and sustained activity against Culex pipiens pallens. Considering the industrialization potential of GO, we believe that GO will play an important role in the pest control and antiepidemic fields.

Environmentally Friendly Zr-Based MOF for Pesticide Delivery: Ultrahigh Loading Capacity, pH-Responsive Release, Improved Leaf Affinity, and Enhanced Antipest Activity.

The stimuli responsive pesticide delivery system (PDS) has drawn increasing attention in recent years, a system which can effectively improve the utilization of pesticides. In the current research, we report a pH responsive PDS by using carboxymethyl cellulose (CMC) modified Zr-based metal organic frameworks (UiO-66-NH2) as the nanocarrier for acetamiprid (ATP). UiO-66-NH2-CMC possesses a large surface area and abundant pores, which can effectively load ATP, and the loading rate is as high as 90.79%. Compared with free ATP, the ATP@UiO-66-NH2-CMC nanopesticide exhibits pH responsive controlled release behavior, and the pesticide can sustained release to the medium. In addition, it also shows improved leaf affinity, which makes it easier to wet the leaf surface and improve the utilization of pesticide. Therefore, ATP@UiO-66-NH2-CMC displays better antipest activity against aphids than free ATP does. Meanwhile, ATP@UiO-66-NH2-CMC shows no negative effects on the germination and growth of maize, showing good biosafety. Moreover, the ATP@UiO-66-NH2-CMC nanopesticide does not contain any toxic organic solvents or additives. Therefore, we hope that it can be a suitable candidate for plant protection and sustainable agriculture.

Metal-Organic Framework (UiO-66)-Based Temperature-Responsive Pesticide Delivery System for Controlled Release and Enhanced Insecticidal Performance against Spodoptera frugiperda.

Spodoptera frugiperda is a global pest that brings about great disasters to crops. Conventional pesticide formulations often suffer from poor water solubility, low stability, burst release, weak leaf adhesion, and low efficiency. To improve the insecticidal activity of pesticides, a stimuli-responsive controlled release pesticide delivery system (PDS) has attracted extensive attention in recent years. This paper reports a temperature-responsive controlled release PDS based on poly(N-isopropyl acrylamide) (PNIPAm)-modified indoxacarb (IDC)-loaded UiO-66-(COOH)2 (IDC@UiO-66-(COOH)2-PNIPAm) and studies its insecticidal activities against S. frugiperda. The UiO-66-(COOH)2 nanocarrier has an excellent pesticide loading performance, and the loading rate for IDC is 78.69%. The as-prepared PDS has good stability, temperature-responsive controllable release performance, and enhanced leaf affinity, so it can effectively improve the utilization rate of IDC. The insecticidal experiment indicates that the PDS has an enhanced control effect against S. frugiperda. In addition, biosafety analysis further verifies that the PDS exhibits no obvious negative effects on the germination of maize seeds and the growth of maize seedlings. In view of this, we believe that this PDS will have a broad application in the field of pesticide formulation innovation, pest management, and sustainable agricultural development.

Chitosan-Heparin Polyelectrolyte Multilayer-Modified Poly(vinyl alcohol) Vascular Patches based on a Decellularized Scaffold for Vascular Regeneration.

Vascular patches play an important role in vascular reparation and cardiovascular diseases therapy. Recently, decellularized scaffold (DCS)-based vascular patches have drawn attention for their good biocompatibility and blood compatibility. In this work, we developed a poly(vinyl alcohol)-coated DCS as a vascular patch for vascular regeneration. Polyelectrolyte multilayers (PEMs) were further decorated on the surface via layer-by-layer (LbL) self-assembly to improve the biocompatibility of the vascular patch. According to the in vitro experiment, the vascular patch exhibited rapid endothelialization and good hemocompatibility. Compared with unmodified poly(vinyl alcohol)/DCS, the PEM-modified vascular patch possesses improved hemocompatibility, for example, enhanced anti-platelet adhesion ability, prolonged in vitro coagulation time, and decreased hemolysis rate. Therefore, this vascular patch is conducive to the proliferation and attachment of endothelial progenitor cells. Meanwhile, the in vivo performance in a porcine model was investigated with the in vivo computed tomography angiography and B ultrasound was used to further confirm the vascular regeneration. Excitedly, the porcine artery could remain unblocked for 5 months after implantation. Our current research provides a potential strategy for treating diseased blood vessels in clinical surgery.

PDA@Ti3 C2 Tx as a novel carrier for pesticide delivery and its application in plant protection: NIR-responsive controlled release and sustained antipest activity.

BACKGROUND: Stimuli-responsive pesticide controlled release system provides a new strategy for the development of high-efficiency pesticides formulation. RESULTS: In this article, we report a novel polydopamine surface modified MXene-Ti3 C2 Tx nanocarrier for pesticide delivery and plant protection. Polydopamine modified Ti3 C2 Tx (PDA@Ti3 C2 Tx ) nanocarrier was prepared by biomimetic self-polymerization of dopamine on the surface of Ti3 C2 Tx . A typical pesticide, emamectin benzoate (EB), was loaded on PDA@Ti3 C2 Tx through physisorption process, with a high pesticide loading rate of 45.37%. PDA@Ti3 C2 Tx exhibited excellent photothermal conversion effect (η = 34.5%). Under the irradiation of near-infrared (NIR) laser, EB would sustained release from PDA@Ti3 C2 Tx nanocarrier to surrounding medium. Compared with free EB, EB@PDA@Ti3 C2 Tx exhibited prolonged persistence period, which can keep antipest activity at 14 days post spraying. In addition, PDA@Ti3 C2 Tx nanocarrier and EB@PDA@Ti3 C2 Tx nanoformulation are of good safety, showing no side effect to the seed germination and seedling growth. CONCLUSION: This research developed a novel nanocarrier for water-insoluble pesticide delivery, realizing NIR-responsive controlled release and sustained antipest activity.

MXene (Ti3C2) Based Pesticide Delivery System for Sustained Release and Enhanced Pest Control.

A multifunctional nanomaterials based pesticide delivery system provides a powerful strategy for the efficient utilization of pesticides. We present here the application of a 2D MXene (Ti3C2) nanomaterial for pesticide delivery and plant protection. Avermectin (AV), a hydrophobic and unstable insecticide, was chosen as the model pesticide. In our study, AV@Ti3C2 was formed by fast adsorption of AV on Ti3C2, with a maximum loading capacity of 81.44%. Compared with hydrophobic AV, AV@Ti3C2 exhibited significantly improved water solubility, which is beneficial for ensuring the bioactivity of pesticide. The AV@Ti3C2 nanoformulation showed pH responsive slow-release behavior, overcoming the burst-release of conventional AV formulations. Besides, AV@Ti3C2 possessed excellent photostability under UV irradiation, which prolonged the persistent period of AV. Therefore, AV@Ti3C2 performed sustaining and enhanced antipest activity, according to the bioactivity assay. Furthermore, AV@Ti3C2 showed satisfactory biosafety, with no negative effect to the germination and growth of maize. Our current research provides a potential candidate, AV@Ti3C2, for pest control, and also broadens the application of 2D MXene materials in plant protection and sustainable agriculture.

Genipin cross-linked carbon dots for antimicrobial, bioimaging and bacterial discrimination.

Multifunctional carbon dots (CDs) present enormous potential in numerous applications and have attracted widespread attention for various applications in the biomedical field. Bacterial infection is a common health issue; the development of antibacterial materials with low toxicity and good biocompatibility is becoming more important. In this work, we synthesized a new type of nitrogen co-doped carbon dots-genipin covalent conjugate (N-CDs-GP) via hydrothermal methods. The microstructure and chemical composition of the N-CDs-GP were characterized. The biocompatibility, stability, antibacterial activity, and fluorescence performance of the N-CDs-GP were assessed. The results revealed that N-CDs-GP possessed high biocompatibility, high light stability, and broad antibacterial activity. Additionally, selective Gram-positive bacterial imaging by N-CDs-GP provided a more rapid method of bacterial detection. The N-CDs-GP have the potential to be applied as bioimaging and antibacterial agents and for bacterial discrimination.

Acceleration of chondrogenic differentiation of human mesenchymal stem cells by sustained growth factor release in 3D graphene oxide incorporated hydrogels.

Damaged articular cartilage has limited self-healing capabilities, leading to degeneration that affects millions of people. Although cartilage tissue engineering is considered a promising approach for treatment, robust and long-term chondrogenesis within a 3-dimensional (3D) scaffold remains a major challenge for complete regeneration. Most current approaches involve incorporation of transforming growth factor-ß (TGF-ß) into the scaffold, but have limited utility owing to the short functional half-life and/or rapid clearance of TGF-ß. In this study, we have tested the incorporation of graphene oxide nanosheets (GO) within a photopolymerizable poly-D, l-lactic acid/polyethylene glycol (PDLLA) hydrogel, for its applicability in sustained release of the chondroinductive growth factor TGF-ß3. We found that with GO incorporation, the hydrogel scaffold (GO/PDLLA) exhibited enhanced initial mechanical strength, i.e., increased compressive modulus, and supported long-term, sustained release of TGF-ß3 for up to 4 weeks. In addition, human bone marrow-derived mesenchymal stem cells (hBMSCs) seeded within TGF-ß3 loaded GO/PDLLA hydrogels displayed high cell viability and improved chondrogenesis in a TGF-ß3 concentration-dependent manner. hBMSCs cultured in GO/PDLLA also demonstrated significantly higher chondrogenic gene expression, including aggrecan, collagen type II and SOX9, and cartilage matrix production when compared to cultures maintained in GO-free scaffolds containing equivalent amounts of TGF-ß3. Upon subcutaneous implantation in vivo, hBMSC-seeded TGF-ß3-GO/PDLLA hydrogel constructs displayed considerably greater cartilage matrix than their TGF-ß3/PDLLA counterparts without GO. Taken together, these findings support the potential application of GO in optimizing TGF-ß3 induced hBMSC chondrogenesis for cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: In this work, we have developed a graphene oxide (GO) incorporated, photocrosslinked PDLLA hybrid hydrogel for localized delivery and sustained release of loaded TGF-ß3 to seeded cells. The incorporation of GO in PDLLA hydrogel suppressed the burst release of TGF-ß3, and significantly prolonged the retention time of the TGF-ß3 initially loaded in the hydrogel. Additionally, the GO improved the initial compressive strength of the hydrogel. Both in vitro analyses and in vivo implantation results showed that the GO/PDLLA constructs seeded with human mesenchymal stem cells (hMSCs) showed significantly higher cartilage formation, compared to GO-free scaffolds containing equivalent amount of TGF-ß3. Findings from this work suggest the potential application of the GO-TGF/PDLLA hydrogel as a functional scaffold for hMSC-based cartilage tissue engineering.

Biomedical application of graphene: From drug delivery, tumor therapy, to theranostics.

The rise of graphene has driven great revolution in various fields, e. g. electronics, device, energy, etc., owing to the well-researched understanding of its physical and chemical properties. In the very recent decade, scientists have poured significant efforts to explore the biological functions of graphene and expand its biomedical applications, including drug delivery, tumor therapy, and theranostics. Encouraged by the inspiring research results and promising contributions of graphene to biomedicine field, herein, we systematically summarize the recent advance of graphene for biomedical application. In this review, we introduce the development of graphene in biomedicine, from drug delivery, tumor therapy, to theranostics. We also demonstrate the surface engineering and multifunctional modification of graphene, and further present the active role of rational decoration in drug delivery, therapy, and theranostic application. In detail, we summarize the surface engineering, active-targeting modification, stimuli-responsive decoration, and their application in anticancer drugs delivery, multiple therapeutic approach, dual-model imaging guided therapy. On the basis of the systematic summary, in the final, we further present the development tendency of graphene in biomedicine, aiming to provide some valuable guidelines for further research.

Quaternized Chitosan-Coated Montmorillonite Interior Antimicrobial Metal-Antibiotic in Situ Coordination Complexation for Mixed Infections of Wounds.

Conventional drug delivery systems for natural clay materials still face critical challenges in their practical application, including multiple bacterial infections, combined infection of bacteria and fungi, and low sterilization efficiency. In this work, we address these challenges using the multifunctional montmorillonite nanosheet-based (MMT-based) drug nanoplatform, which involves the antibiotic 5-fluorocytosine (5-FC), antibacterial metal copper ions, and quaternized chitosan (QCS). Composite material QCS/MMT/5-FCCu can can strongly inhibit Staphylococcus aureus (a typical Gram-positive bacterium), Escherichia coli (a typical Gram-negative bacterium), and Candida albicans (a fungus) because 5-FC coordinates with copper ions in situ and due to the deposition of QCS. The subsequent drug release behavior of 5-FCCu was studied, and the results show an initial high concentration kills microorganisms and long-acting sustained release inhibition. Moreover, in vivo wound experiments and toxicity experiments show the promotion of wound healing and excellent biocompatibility. As a demonstration of the utility of the latter, we have shown that the MMT-based smart platform can be used for the treatment of mixed infections of wounds.

Hyaluronic Acid-Modified Porous Carbon-Coated Fe3O4 Nanoparticles for Magnetic Resonance Imaging-Guided Photothermal/Chemotherapy of Tumors.

Chemotherapy is an effective method for treating cancer, clinically. However, side effects of drug and multidrug resistance restrict its application. In recent years, the combined treatment of chemotherapy and photothermal therapy (PTT) is becoming a promising method for treating cancer. PTT utilizes nanomaterials absorbing near-infrared light and producing heat to acquire advanced hyperthermia strategy for cancer treatment. Carbon nanomaterials with good biocompatibility, high surface area, and excellent photothermal properties are an excellent nanoplatform for drug delivery and PTT. Herein, porous carbon-coated magnetite nanoparticles (PCCMNs) were successfully synthesized by a one-pot solvothermal method. Magnetite, a contrast agent, can be used for magnetic resonance imaging. Hyaluronic acid was used to modify the PCCMNs to achieve targeted therapy. The obtained nanohybrid with a good photothermal effect can realize combined PTT/chemotherapy and will be a promising nanoplatform for high efficacy theranostics.

Carboxymethyl Chitosan Modified Carbon Nanoparticle for Controlled Emamectin Benzoate Delivery: Improved Solubility, pH-Responsive Release, and Sustainable Pest Control.

Environmentally friendly pesticide delivery systems have drawn extensive attention in recent years, and they show great promise in sustainable development of agriculture. We herein report a multifunctional nanoplatform, carboxymethyl chitosan modified carbon nanoparticles (CMC@CNP), as the carrier for emamectin benzoate (EB, a widely used insecticide), and investigate its sustainable antipest activity. EB was loaded on CMC@CNP nanocarrier via simple physisorption process, with a high loading ratio of 55.56%. The EB@CMC@CNP nanoformulation showed improved solubility and dispersion stability in aqueous solution, which is of vital importance to its practical application. Different from free EB, EB@CMC@CNP exhibited pH-responsive controlled release performance, leading to sustained and steady EB release and prolonged persistence time. In addition, the significantly enhanced anti-UV property of EB@CMC@CNP further ensured its antipest activity. Therefore, EB@CMC@CNP exhibited superior pest control performance than free EB. In consideration of its low cost, easy preparation, free of organic solution, and enhanced bioactivity, we expect, CMC@CNP will have a brilliant future in pest control and green agriculture.

HP-ß-CD Functionalized Fe3O4/CNPs-Based Theranostic Nanoplatform for pH/NIR Responsive Drug Release and MR/NIRFL Imaging-Guided Synergetic Chemo/Photothermal Therapy of Tumor.

The combination of chemotherapy and photothermal therapy has aroused great interest due to its better antitumor effect than either single therapy alone. Herein, we report on the development of hydroxypropyl-ß-cyclodextrin functionalized Fe3O4/carbon nanoparticles (HFCNPs) for pH/near-infrared (NIR) responsive drug release, magnetic resonance/NIR fluorescence (MR/NIRFL) imaging-guided combined chemo/photothermal therapy. The high doxorubicin (DOX) loading capacity (61.2%) and controlled drug release by NIR irradiation and weak acid microenvironment render HFCNPs a good vector for DOX delivery and controlled release. Moreover, the MR/NIRFL dual-modal imaging was used to define the tumor location, size, and boundary and to track the tumor accumulation of HFCNPs and their biodistribution. The efficient accumulation and prolonged retention time of the nanoparticles in tumor are beneficial to tumor therapy. Taking advantage of the NIR laser-induced heating and hence promoted drug permeation, remarkable tumor inhibition was realized by synergetic chemo/photothermal therapy. In conclusion, the current work offers a promising approach to the development of smart and efficient multimodal cancer-targeted nanotheranostics.

Graphene Oxide Incorporated PLGA Nanofibrous Scaffold for Solid Phase Gene Delivery into Mesenchymal Stem Cells.

Delivery of functional genes into stem cells shows great application prospect in DNA-based tissue engineering. However, comparing with epithelial cells and cancer cells, stem cells usually exhibit low gene transfection efficiency. To enhance the transfection efficiency, non-viral gene delivery in combination with biomaterial scaffolds, has raised increasing interests from researchers in tissue engineering. Nanofibers fabricated by electrospinning technique mimicking extracellular matrix (ECM) are widely used in tissue engineering applications. In addition, graphene oxide (GO) with ultrahigh specific surface area and ultra-strong adsorption capability, is an ideal candidate for gene delivery. In this work, polyethylenimine (PEI)/plasmid DNA-GO/poly(D,L-lactic-co-glycolic acid) (PLGA) scaffold was developed as a substrate for solid phase gene delivery and a tissue engineering substrate for stem cells growth and differentiation. In order to improve the transfection efficiency of stem cells, PEI/pDNA complexes were immobilized at the surface of electropun GO incorporated PLGA nanofibrous mat. Human embryonic kidney 293 cells and human umbilical cord derived mesenchymal stem cells cultured on PEI/pDNA-GO/PLGA scaffold showed significantly higher green fluorescent protein (GFP) expression than PEI/pGFP in the medium. These findings demonstrated that solid phase gene delivery using PEI/pDNA-GO/PLGA significantly enhanced the gene transfection efficiency, and may find potential application of gene therapy and regeneration medicine.

Chondroinductive factor-free chondrogenic differentiation of human mesenchymal stem cells in graphene oxide-incorporated hydrogels.

Graphene-based nanomaterials have been applied as biomaterials to enhance stem cell adhesion, growth and differentiation by serving as nanocarriers for growth factors or other small molecules. However, the direct effect of graphene oxide (GO) itself on stem cells, in the absence of exogenous differentiation inductive factors, has not been tested. In this study, we loaded GO nanosheets and human bone marrow-derived mesenchymal stem cells (hBMSC) into a photopolymerizable poly-d,l-lactic acid/polyethylene glycol (PDLLA) hydrogel, a robust chondrosupportive scaffold recently developed in our laboratory, and assessed hBMSC differentiation along the chondrogenic lineage without supplemental chondroinductive factors. We first examined the effect of GO incorporation on the mechanical properties of constructs, and observed that the GO-containing constructs (GO/PDLLA) exhibited enhanced compressive modulus in a GO concentration dependent manner. hBMSCs cultured in GO/PDLLA maintained high cell viability (>95%), indicating minimal cytotoxicity of GO. Importantly, compared to those encapsulated in PDLLA hydrogel, hBMSCs within GO/PDLLA showed significantly higher level of gene expression of the cartilage matrix genes, aggrecan and collagen type II, and produced more cartilage matrix. In addition, the pro-chondrogenesis effect of GO increased with increasing GO concentration. Immunohistochemical results suggested that GO-enhanced hBMSC chondrogenesis was correlated with enriched sequestration of insulin, a necessary supplement known to have pro-chondrogenesis effects on hBMSC. Taken together, these findings demonstrate the utility of using GO to improve the mechanical properties and chondrogenic differentiation state of MSC-laden, engineered hydrogel constructs, without the use of exogenous growth factors, thus representing a potentially promising, biologics-free approach for cartilage tissue engineering.